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The Journal of Immunology, 2005, 175: 1884-1893.
Copyright © 2005 by The American Association of Immunologists

The Inflammatory versus Constitutive Trafficking of Mononuclear Phagocytes into the Alveolar Space of Mice Is Associated with Drastic Changes in Their Gene Expression Profiles 1

Mrigank Srivastava*, Steffen Jung{ddagger}, Jochen Wilhelm{dagger}, Ludger Fink{dagger}, Frank Bühling§, Tobias Welte, Rainer M. Bohle{dagger}, Werner Seeger*, Jürgen Lohmeyer* and Ulrich A. Maus2,*

* Department of Internal Medicine, Division of Pulmonary and Critical Care Medicine and {dagger} Department of Pathology, Justus-Liebig-University, Giessen, Germany; {ddagger} Department of Immunology, The Weizmann Institute of Science, Rehovot, Israel; § Institute of Immunology, Otto-von-Guericke University, Magdeburg, Germany; and Department of Pulmonary Medicine, Hannover School of Medicine, Hannover, Germany

Mononuclear phagocytes enter the lungs both constitutively to maintain alveolar macrophage and dendritic cell homeostasis, as well as during lung inflammation, where the role of these cells is less well defined. We used a transgenic mouse strain (CX3CR1+/GFP) that harbors a GFP label in circulating monocytes to identify and sort these cells from the vascular and alveolar compartments under both constitutive and acute lung inflammatory conditions. Using nylon arrays combined with real-time RT-PCR for gene expression profiling, we found that flow-sorted, highly purified mononuclear phagocytes recruited to acutely inflamed mouse lungs showed strongly up-regulated mRNA levels of the neutrophil chemoattractants KC, MIP-2, and IP-10, which contrasted with alveolar mononuclear phagocytes that immigrated in steady state. Similar observations were made for the lysosomal cathepsins B, L, and K being strongly up-regulated in mononuclear phagocytes upon recruitment to inflamed lungs but not during constitutive alveolar immigration. Inflammatory elicited mononuclear phagocytes also demonstrated significantly increased mRNA levels of the cytokine TNF-{alpha} and the PRR-associated molecules CD14, TLR4, and syndecan-4. Together, inflammatory elicited mononuclear phagocytes exhibit strongly increased neutrophil chemoattractants, lysosomal proteases, and LPS signaling mRNA transcripts, suggesting that these cells may play a major role in acute lung inflammatory processes.




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